Synthesis of nanoparticles coming into focus

FAYETTEVILLE, Ark.  Scientists are fast gaining control over the building of tiny particles, accomplishing nanoparticle synthesis in both inorganic and organic chemistries. University of Arkansas researchers here have devised a "green" chemical process that offers tight control over the size of nanoparticles and eliminates toxic by-products. And a team at the University of Michigan (Ann Arbor) is developing dendrimer-based fluorescent particles to monitor human cell damage from radiation.

Under a $2 million NASA grant, the Michigan team will develop a method of implanting optically active nanoparticles inside white blood cells, suggesting that medical applications may be an immediate practical application for nanotechnology.

Experiments at the University of Arkansas' Nanofabrication Group are revealing ways to direct the course of basic inorganic-crystal formation using insights into the surface chemistry of nanoparticles. "We have a green method of synthesizing crystalline nanocrystals," said Xiaogang Peng, assistant professor in the Department of Chemistry and Biochemistry. "The tunable reactivity of our monomers provides the necessary balance between nucleation and growth, and that is the key for controlling their size and the distribution of different sizes." The work was performed with William Yu, a postdoctoral research associate.

Though crystal formation has been well-studied in bulk materials, the process of growing nanoscale crystal particles is in its infancy. One important difference for nanoscale crystals is the large surface area of a particle in relation to the bulk of the crystal. Unlike in bulk crystals, energetic interactions at this surface can strongly influence the nanocrystal growth process.

No toxic by-products

The Arkansas experiments have produced II-VI semiconductor nanocrystals similar to silicon nanoclusters, but with a uniform size distribution and in a "green" manner  that is, without any toxic by-products. By using an alternative chemical synthesis route that eliminates all such by-products, Peng and his colleagues have arrived at a synthesis method that Peng claims is simpler, less expensive and above all more "user-friendly." It should be easily reproducible by other researchers, said Peng, whose personal hope is to foster a greening of nanotechnology.

"Our conclusion is that if you look hard from the very beginning, you can find green methods of synthesizing nanocrystals or any other nanoscale technology," he said.

Peng's method varies ligand concentration during layered-growth phases of crystal formation. Ligands are short-chain molecules that can interact at the surface to influence the growth process. Tuning the reaction creates a simple cookbooklike schedule to optimize the overall chemical reaction to simultaneously maximize the number of nanoparticles and provides a uniform size distribution.

In an experiment to verify that the method works, Peng grew cadmium-selenium nanocrystals that were one of 10 quantum steps in size, color and intensity. In addition, the outer ligands created a monodisperse (20 percent) spacing between the particles. The 10 nanocrystal sizes varied from 2 to 5.3 nanometers, each fluorescing at a different wavelength between 380 and 450 nm.

Colloidal semiconductor nanocrystals  quantum dots, nanoparticles and nanoclusters  are nanometer-size crystallites whose tiny size accounts for their unusual properties, such as fluorescing where the bulk version does not. Researchers like Munir Nayfeh, a professor at the University of Illinois, have demonstrated nanometer-scale silicon spheres containing only 29 silicon atoms, making them highly fluorescent blue. Nayfeh also showed a 2.5-nm particle that produced yellow light and one at 2.9 nm that produced red light. A 1.67-nm particle with just 123 atoms glowed a bright green under UV excitation.

Nanoparticles exhibit unusual physical effects such as light emission because their electrons are confined in an area that is smaller than Bohr's radius  the natural distance between electron-hole pairs. By stimulating these nanoparticles with low-energy radiation in the ultraviolet region of the spectrum while their electron-hole pairs are thus confined, they store more energy than their usual quantum states allow. The resulting emissions are shifted to visible wavelengths, so that attaching them to specific human drugs or antibodies allows them to be used as biological markers.

Organic-chemistry work

An approach that also uses ligand chemistry to create nanoparticles, but in the context of organic chemistry, is the new field of dendrimer chemistry. With dendrimers, the ligands themselves organize into a regular structure that results from dendritic growth that emanates from a central molecule. The basic chemistry is the same polymerization process that creates plastics and nylon, but like Peng's green inorganic reactions, the result is compact and uniform nanoparticles.

Dendrimer creation starts with a simple seed particle such as a molecule of ammonia. The basic precursor units of polymers, monomers such as acrylic acid and a diamine bind to the ammonia molecule to form the first-generation shell of a dendrimer. The ends of these monomers become binding sites for more monomers, creating a second-generation shell, resulting in a structure that branches out in three dimensions like a spherical tree. Subsequent reac-tion cycles continue to add more shells and the geometry of each particle is identical, distinguishing dendrimers from other polymer forms, which are typically jumbled assemblages of long-chain polymer molecules.

The spherical surface of a dendrimer acts like a microscopic form of Velcro, and a variety of substances can bind to the surface. As the successive shells form they alternately expose amines and acids on their surface, so that each type of site is available for further attachment of molecules or other nanocomponents. In the case of the new work to be done under the NASA grant at Michigan's Center for Biologic Nanotechnology, fluorescent molecules will be attached to the surface of dendrimers. Simply ingesting or inhaling a solution of these tailored molecules will allow them to find their way into white blood cells in the bloodstream.

The particular fluorescent molecules being used glow only in the presence of proteins associated with cell death. Once inside the cells, the dendrimers would become real-time monitors of radiation exposure or infection, both of which result in the death of white blood cells.

The team plans to develop a laser-based retinal scanner to detect the fluorescent particles inside the white blood cells as they pass through blood vessels in the retina. An astronaut would look into the scanner for about 15 seconds to detect any glowing nanoparticles that indicate problems inside his or her white blood cells. A retinal scanner is ideal for the job, because the blood cells have to go through the retinal capillaries in single file, so each can be separately checked for fluorescence.

Early alarm

Radiation changes the flow of calcium ions inside the white blood cells, said James Baker, director of the Center for Biologic Nanotechnology, eventually triggering irreversible damage even if each individual dose is within accepted limits. By constantly monitoring the white blood cells, the real health of the cell can be checked, to raise alarms before such damage occurs.

Baker said that NASA chose his team because of its previous successes with contracts from the National Cancer Institute, for which the group developed intracellular dendrimers to detect the onset of precancerous changes inside living cells before they turned malignant.

The NASA project is part of a larger program whose goal is building a comprehensive biomonitoring system using dendrimers. Researchers are currently creating a library of biologically active nanocomponents that will serve as building blocks for complex nanomachines called "tecto-dendrimers." They have identified five biomonitoring operations they would like their nanobots to perform: diseased-cell recognition (as in the NASA project), diagnosis of disease states, drug delivery, location reporting and reporting the outcome of therapy. The project has produced proof-of-concept prototypes that perform four of the operations.  Additional reporting by Chappell Brown